Hypothalamic-amygdala gating of caregiving-like prosocial behavior in mice
Kai-Wen Geng, Rui-Rui Wang, Yan Yang, Yan Wang, Ting He, Chun-Li Li, Chong-Shun Xu, Jun Chen
Kai-Wen Geng, Rui-Rui Wang, Yan Yang, Yan Wang, Ting He, Chun-Li Li, Chong-Shun Xu, Jun Chen
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Research Article Cell biology Neuroscience

Hypothalamic-amygdala gating of caregiving-like prosocial behavior in mice

Abstract

Distress sharing within an ingroup instinctively motivates caregiving-like prosocial behavior in social animals and humans, yet how aversive social stimuli paradoxically trigger such behavior remains unclear. Here, we show that stress-state matching in observer mice elicits caregiving-like behaviors (allogrooming and injury-targeted allolicking) toward cagemates in pain, resulting in synchronized social buffering. Importantly, we identify that the excitation of vasopressin receptor 1a–expressing (V1aR-expressing) neurons in the central medial amygdala (CeM) underlies both emotional-state matching and subsequent allogrooming/allolicking. This excitation is accomplished by arginine vasopressin (AVP) release from presynaptic terminals of the hypothalamic paraventricular nucleus (PVN) to act specifically on postsynaptic V1aR in the CeM. The CeMV1aR neurons then project to the ventral tegmental area (VTA) to drive caregiving-like actions through positive reinforcement, manifested as prosocial preference and recurrent allogrooming/allolicking, and to produce anxiolysis in the caregiver. Collectively, we unravel a dedicated trisynaptic PVNAVP-CeMV1aR-VTA circuit driving and gating caregiving-like behaviors and advance the mechanistic understanding of AVP-V1aR signaling in prosociality.

Authors

Kai-Wen Geng, Rui-Rui Wang, Yan Yang, Yan Wang, Ting He, Chun-Li Li, Chong-Shun Xu, Jun Chen

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Figure 4

CeMV1aR neurons drive general and targeted caregiving-like behavior.

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CeMV1aR neurons drive general and targeted caregiving-like behavior. (A ...
(A and B) Schematic of viral injections and representative images showing V1aR mRNA expression (A) and statistics (B). (C) Representative raster plots depicting social investigation, allogrooming, and allolicking in eYFP and taCasp3 mice during the prosocial interaction. (D–F) Latency (D), time (E), and bouts (F) of allogrooming/allolicking toward pain-suffering cagemates of both eYFP and taCasp3 observers. (G–I) Heatmaps of locomotor activity (G), exploration time (H), and preference index (I) of both eYFP and taCasp3 mice in social affective preference (SAP) test. (J) Schematic for CeM injections and fiber implantations (left), and a representative image showing ChR2-eYFP expression (right) in the CeM. (K and L) Probability (K) and duration (L) of evoked allogrooming/allolicking toward naive or melittin-treated cagemates during opto-activation (17 s) in eYFP versus ChR2 mice. (M) Percentage of trials in each eYFP and ChR2 mice with evoked allogrooming/allolicking during opto-activation. (N) Schematic for CeM injections and fiber implantations (left), and a representative image showing GtACR2-eGFP expressions (right) in the CeM. (O) Whole-cell voltage clamp showing light-mediated silencing of CeMV1aR neurons in an acute slice preparation. (P–R) Example raster plots (P), probability (Q), and duration (R) of spontaneous allogrooming/allolicking toward pain-suffering cagemates during opto-inhibition (10 s) in eYFP and GtACR2 observers. Scale bar: 100 μm (A, J and N). All mice are male. n = 52–98 trials from 4–5 mice in K–M and P–R. Other n values are indicated in the figure. Statistical results are included in Supplemental Table 2. Mean ± SEM in B, D–F, H, I and M. Box and whiskers (center line, median; box limits, quartiles; whiskers, 1.5 × interquartile range; points, outliers) in L and R. Unpaired t test B, D, F, and I; Mann Whitney U test for E and R; Paired t test for H; Kruskal-Wallis test with Dunn’s multiple comparisons for L; 2-way ANOVA with Tukey’s multiple comparisons for M.